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Modified peptidoglycan precursors produced by glycopeptide-resistant enterococci
1Department of Biochemistry, University of Cambridge, UK.
FEMS Microbiology Letters
|July 1, 1992
Summary
Vancomycin resistance in Enterococcus faecium is linked to altered peptidoglycan precursors. A modified precursor containing D-lactate instead of D-alanine hinders vancomycin binding, enabling bacterial survival.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Vancomycin is a crucial antibiotic for treating Gram-positive bacterial infections.
- Emergence of vancomycin-resistant Enterococcus faecium (VRE) poses a significant public health threat.
- Understanding resistance mechanisms is vital for developing new therapeutic strategies.
Purpose of the Study:
- To investigate the biochemical basis of vancomycin resistance in Enterococcus faecium.
- To identify modifications in cytoplasmic peptidoglycan precursors contributing to resistance.
Main Methods:
- Purification of cytoplasmic peptidoglycan precursors from vancomycin-sensitive and -resistant Enterococcus faecium strains.
- Mass spectrometry to identify the chemical structure of the modified precursor.
- Enzymatic assays to confirm the role of D-lactate dehydrogenase.
Main Results:
- Vancomycin-resistant strains produced a modified peptidoglycan precursor: UDP-MurNAc-L-Ala-D-Glu-L-Lys-D-Ala-D-lactate.
- The D-lactate residue at the terminal position was confirmed by mass analysis and enzymatic activity.
- This modification hinders vancomycin-precursor complex formation but allows peptidoglycan synthesis.
Conclusions:
- Vancomycin resistance in Enterococcus faecium is mediated by the synthesis of a D-lactate-containing peptidoglycan precursor.
- This structural alteration confers resistance by preventing vancomycin binding to its target.
- The findings provide insights into antibiotic resistance mechanisms and potential targets for novel drugs.